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Andrew Schorr:

Hello and welcome to Patient Power. I'm Andrew Schorr in San Diego. We're joined by Dr. Richard Furman from
Weill Cornell Medical College in New York City, a leading expert in CLL, to
really discuss in light of a new drug approval in CLL, where do we go from
here? What does it mean for the CLL
community as we try to have more patients, including, of course, people with
the most serious forms of CLL or complications from CLL, do better? Dr. Furman, welcome to back to Patient
Power.

Dr. Furman:

Thank you very much for having me.

Andrew Schorr:

So now we have a new drug approved, a powerful
new drug, and you have others that you've had in approvals over the last year
or so. You have drugs that are injected
and pills we take. Now, where are we now
in trying to help more people with the addition of venetoclax (Venclexta)?

Dr. Furman:

So venetoclax is just an additional tool for
physicians to use, and it provides a very effective and extremely well
tolerated medication for the treatment of patients with CLL. What really is so important about the current
approval for venetoclax is that the original trials were actually plagued by
two deaths due to tumor lysis syndrome.
What I really think is very important for everyone to understand is the
methodology or the process for administering the pills back then was very
different than what we do now.

And we currently do what's called a ramp?up dose schedule
where you start off at 20 milligrams then go to 50, 100, 200 and 400, basically
a week at that time as long as you don't show any evidence of having tumor
lysis on your laboratory values. And
since this has been instituted, we've actually not had any cases of clinically
significant tumor lysis. So some
patients have had laboratory abnormalities consistent with tumor lysis, but
none of them met the criteria for being clinically significant.

So we're now, you know, basically have made venetoclax—or
figured out how to use venetoclax, which is a highly effective tool,
safely. And so it now joins the ranks of
ibrutinib (Imbruvica) and idelalisib (Zydelig) as something that really will
have a tremendous hopefully in the longevity of CLL patients.

Andrew Schorr:

So the question is, and we've talked about this
at some of your medical conferences, is combining an agent with another one,
you get a synergistic effect, and would that be important for some patients?

Dr. Furman:

So I think the most important data to look at is
actually the ibrutinib 1102 data. So
this is the first Phase II study that we did with ibrutinib, and it started
over about four years ago. And we treated 31 patients who were treatment?naive
who needed therapy and were over the age of 65, with ibrutinib as their first
treatment. So [this was] a group of
patients who needed therapy, and when they got ibrutinib as their first therapy
actually only one patient has progressed out of those 31 patients while on
ibrutinib.

And this one patient was a 17p-deleted patient who developed
a Richter's syndrome at month 8. So
arguably the Richter's was there before the treatment began and was just
unmasked by the ibrutinib. So in
essence, if you aren't 17p, and I think the same is probably true for 11q as
well as some other genetic lesions, and you get ibrutinib when you need
treatment based on the standard criteria, the current data suggest that that's
all you need. So these are a group of
patients who don't need anything else.

Now, with that being said, we have data at least with
ibrutinib plus rituximab and ibrutinib plus bendamustine (Treanda)-rituximab
that really indicate that the chemotherapy and the immunotherapy don't enhance
the outcome of patients who are receiving ibrutinib. And I think that that's the overwhelming,
most important piece of information for everyone to remember so that even the
combination chemotherapy plus ibrutinib is no better than ibrutinib alone. And so there's no need to assume excess
risk.

With that being said, there are small groups of patients
like the 17p-deleted patients, the 11q deleted patients or the NOTCH1-mutated
patients who have a particularly high risk of developing a transformation or
genomic instability that might lead to them developing a mutation that would
make them resistant to ibrutinib. These
patients may derive benefit from being put into a complete response quicker,
and just the idea of removing the number of cells that are present as quickly
as possible diminishes the chance of having one of these secondary hits occur
that gives rises to either a Richter's or a resistance—or a mutation that
causes resistance to ibrutinib.

And so that's where venetoclax really might be so helpful,
because it really does induce very deep remissions very quickly. And so in that population of patients there
really does seem to be a potential benefit of adding venetoclax to
ibrutinib.

Andrew Schorr:

So do you think the bottom line of where we are
now is you have more tools, if you will, is that a wider array of CLL patients,
whether they've been previously treated or they're diagnosed with the more
aggressive form of CLL, that you have something for them to give them
hope?

Dr. Furman:

Absolutely.
I mean I think, you know, ibrutinib and idelalisib are wonderful agents,
and I think venetoclax is just an additional agent to that armamentarium. The thing that's I think important to keep in
mind is the data for venetoclax is going to evolve over time, so we are in a
position now where we're having what are called MRD?negative partial
responses.

So typically partial responses should be, you know, patients
with persistent lymphadenopathy and obviously some bone marrow involvement or
what?not. But what we're finding with venetoclax is patients are having lymph
node sizes, you know, two to three centimeters in size and aren't having any
evidence of CLL in the peripheral blood or the bone marrow. So these MRD?negative partial responders
really are doing wonderfully. And, in
fact, the MRD negativity rate is more predictive than the iwCLL response, or
the partial response designation.

So right now the data, because of how it was collected, not
considering that, is really going to be representative of the true potential of
venetoclax. And I think that what we'll find is that the PFS, the progression?free
survival, of these patients who just have partial responses will be quite long,
and that's really the important piece of information for the patients. And I think that that's information that will
evolve over the next year or two, and subsequent studies will include this
whole idea about potentially being MRD negative and still being in a partial
response.

Andrew Schorr:

Right. So,
of course, the bottom line for any of us living with CLL is how do we
feel.

Dr. Furman:

Right.

Andrew Schorr:

We can do what we want to do with our lives, and,
you know, you may see CLL in our blood or in our bone marrow, but if it's not
affecting us greatly, we're doing well.

Dr. Furman:

But just to I think clarify though, the lymph
nodes in these patients who are MRD negative and they have a partial response
are probably just scar or probably just other inflammatory cells and not
CLL. So I think these are a group of
patients who might be cleared of their disease even though they're only in a
partial response. And so it really makes
it—you know, I think it basically underestimates how wonderful the data really
is.

Andrew Schorr:

Wow. Well,
of course, we cover your big medical meetings that you have and I know when we
get to ASH in December of 2016 we'll hear even more. Dr. Richard Furman, I want to thank you
for your leadership in research and working with your colleagues around the
world to help move this forward for us.
And I want to thank you for being with us to help us understand how
adding a new drug and the ongoing studies and maybe understanding assessment
criteria, like what you were just talking about, can help us really know the
value of what we have and where we're headed.
Thanks for being with us, Dr. Furman.

Dr. Furman:

My pleasure.

Andrew Schorr:

Okay.
Andrew Schorr with an update from a leading investigator in New York
City, Dr. Richard Furman.

Remember, knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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